title: Multifunctional nanomedicine platform for concurrent delivery of chemotherapeutic drugs and mild hyperthermia to ovarian cancer cells.
abstract: A multifunctional tumor-targeting delivery system was developed and evaluated for an efficient treatment of drug-resistant ovarian cancer by combinatorial therapeutic modality based on chemotherapy and mild hyperthermia. The engineered iron oxide nanoparticle (IONPs)-based nanocarrier served as an efficient delivery vehicle for doxorubicin and provided the ability to heat cancer cells remotely upon exposure to an alternating magnetic field (AMF). The nanocarrier was additionally modified with polyethylene glycol and LHRH peptide to improve its biocompatibility and ability to target tumor cells. The synthesized delivery system has an average size of 97.1 nm and a zeta potential close to zero, both parameters favorable for increased stability in biological media and decreased elimination by the immune system. The nanocarrier demonstrated faster drug release in acidic conditions that mimic the tumor environment. It was also observed that the LHRH targeted delivery system could effectively enter drug resistant ovarian cancer cells, and the fate of doxorubicin was tracked with fluorescence microscope. Mild hyperthermia (40°C) generated by IONPs under exposure to AMF synergistically increased the cytotoxicity of doxorubicin delivered by the developed nanocarrier to cancer cells. Thus, the developed IONPs-based delivery system has high potential in the effective treatment of ovarian cancer by combinatorial approach.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 1601 SW Jefferson Street, Corvallis, OR 97331, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Taratula
authors.forename: Raj Kumar
authors.initials: RK
authors.lastname: Dani
authors.forename: Canan
authors.initials: C
authors.lastname: Schumann
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Andrew
authors.initials: A
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Song
authors.forename: Pallavi
authors.initials: P
authors.lastname: Dhagat
authors.forename: Oleh
authors.initials: O
authors.lastname: Taratula
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry; D005334:Fever / Q000188:drug therapy*; D006801:Humans; D008280:Magnetics; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D050997:Nanomedicine / Q000379:methods; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005290:Ferric Compounds; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D011092:Polyethylene Glycols
keywords: Alternating magnetic field (AMF); Combinatorial treatment; Doxorubicin; Iron oxide nanoparticles; Mild hyperthermia; Ovarian cancer